Reagents and Methods for Monitoring Breast Cancer Therapy

Abstract

Disclosed herein are compositions including reagents for detecting human autoantibodies against at least two proteins selected from the group consisting of A1AT, ANGPTL4, LRP10, GFRA1, LGALS3, CST2, DKK1, CAPC, GRP78, and GRN, wherein at least one of the antibody detection markers is selected from the group consisting of A1AT, LGALS3, and CAPC, and their use in monitoring efficacy of breast cancer therapy and breast cancer recurrence.

We claim: 
     
         1 . A composition comprising at least 2 antibody detection markers, wherein the antibody detection markers comprise reagents for detecting human autoantibodies against at least two proteins selected from the group consisting of A1AT (Alpha-1 antitrypsin) (SEQ ID NO:7), ANGPTL4 (Angiopoietin-like 4) (SEQ ID NO:1), LRP10 (LDL Receptor Related Protein 10) (SEQ ID NO:5), GFRA1 (GDNF Family Receptor Alpha 1) (SEQ ID NO:3), LGALS3 (Galectin-3) (SEQ ID NO:8), CST2 (Cystatin SA) (SEQ ID NO:6), DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1) (SEQ ID NO:2), CAPC (Cytokeratin-Associated Protein In Cancer) (SEQ ID NO:9), GRP78 (78 kDa glucose-regulated protein) (SEQ ID NO:12) and GRN (Granulin) (SEQ ID NO:4), wherein at least one of the proteins is selected from the group consisting of A1AT, LGALS3, and CAPC. 
     
     
         2 . The composition of  claim 1 , wherein the composition includes reagents for detecting human autoantibodies against at least 3 proteins selected from the group consisting of A1AT, ANGPTL4, LRP10, GFRA1, LGALS3, CST2, DKK1, CAPC, GRP78, and GRN. 
     
     
         3 . The composition of  claim 1 , wherein the composition includes reagents for detecting human autoantibodies against at least 5, 6, 7, 8, or all 9 proteins in the recited group. 
     
     
         4 . The composition of  claim 1 , wherein the composition consists of between 2 and 1000 antibody detection markers. 
     
     
         5 . The composition of  claim 1 , wherein the composition consists of between 4 and 500 antibody detection markers. 
     
     
         6 . The composition of  claim 1 , wherein the composition includes reagents for detecting human autoantibodies against at least 2 of ANGPTL4, GFRA1, LGALS3, DKK1 and GRN. 
     
     
         7 . The composition of  claim 1 , wherein the composition includes reagents for detecting human autoantibodies against at least 3, 4, or all 5 of ANGPTL4, GFRA1, LGALS3, DKK1 and GRN. 
     
     
         8 . The composition of  claim 1 , wherein the reagents for detecting human autoantibodies comprise the at least two proteins, or antigenic fragments thereof. 
     
     
         9 . The composition of  claim 8 , wherein the at least two proteins or antigenic fragments thereof comprise native extracellular domains and/or native secreted proteins or antigenic fragments thereof. 
     
     
         10 . The composition of  claim 1 , wherein the reagents are detectably labeled. 
     
     
         11 . The composition of  claim 8 , wherein the at least two proteins, or antigenic fragments thereof, are expressed as a fusion with a detectable domain, including but not limited to an Fc domain. 
     
     
         12 . The composition of  claim 1 , wherein the reagents are immobilized on a surface of a solid support. 
     
     
         13 . A method for monitoring breast cancer therapy, comprising
 (a) contacting a bodily fluid sample from a subject who is undergoing or has undergone breast cancer therapy with one or more reagents for detecting autoantibodies against one or more proteins selected from the group consisting of A1AT, ANGPTL4, LRP10, GFRA1, LGALS3, CST2, DKK1, CAPC, GRP78, and GRN; and   (b) determining an amount of autoantibodies against the one or more proteins in the bodily fluid sample;   wherein a decrease in the amount of autoantibodies relative to a control, such as a baseline level of autoantibodies in a similar bodily fluid sample from the subject indicates efficacy of the breast cancer therapy in the subject.   
     
     
         14 . A method for prognosing breast cancer recurrence, comprising
 (a) contacting a bodily fluid sample from a subject who has received breast cancer therapy with one or more reagents for detecting autoantibodies against one or more proteins selected from the group consisting of A1AT, ANGPTL4, LRP10, GFRA1, LGALS3, CST2, DKK1, CAPC, GRP78, and GRN; and   (b) determining an amount of autoantibodies against the one or more proteins in the bodily fluid sample;   wherein an increase in the amount of autoantibodies relative to a baseline level of autoantibodies in a control, such as a similar bodily fluid sample from the subject indicates a likelihood of breast cancer recurrence in the subject.   
     
     
         15 . The method of  claim 13 , wherein the reagents comprise reagents for detecting autoantibodies 3 or more of the recited proteins. 
     
     
         16 . The method of  claim 13 , wherein the reagents comprise reagents for detecting autoantibodies against 5, 6, 7, 8, or all 9 of the recited proteins. 
     
     
         17 . The method of  claim 13 , wherein the one or more reagents comprise at least 2 proteins, or antigenic fragments thereof, selected from the group consisting of ANGPTL4, GFRA1, LGALS3, DKK1 and GRN. 
     
     
         18 . The method of  claim 13 , wherein the one or more reagents comprise at least 3, 4, or all 5 proteins, or antigenic fragments thereof, selected from the group consisting of ANGPTL4, GFRA1, LGALS3, DKK1 and GRN.